Flashcards in Hepatitis and Cirrhosis Deck (97):
- aminotransferases: ALT & AST
- serum albumin
What are impt hx ?s to ask if you are concerned about liver disease?
- exposure to chemicals, meds, herbs
- accompanying sxs
- parenteral exposure
- IV and intranasal drug use
- tattoos and piercings
- sexual activity
- travel and exposure hx
- ETOH hx
PE findings that suggest liver disease?
- cachexia: malnourishment (drinks a lot, drug user)
- stigmata of longstanding liver disease
- signs of alcoholic liver disease: acutely - large, if cirrhotic - small
- enlarged L supraclavicular node - HCC
- JVP suggests RHF secondary portal HTN
- R pleural effusion in absence of advanced ascited can be seen in cirrhosis (this can cause portal HTN)
What is autoimmune hepatitis? Type 1 and type 2?
- chronic hepatitis: pp isn't well understood
type 1 (classic): occurs in women of all age groups
type 2 (ALKM-1): occurs in girls and young women
- characterized by circulating autoabs (not thought to be part of pp)
- high levels of serum globulin concentrations
Clinical manifestations of autoimmune hepatitis?
- can be asx
- subclinical and those presenting with advanced cirrhosis
- fulminant hepatitis
presence of serological markers
generally aminotransferases more elev than bili and AP
Extrahepatic manifestations of autoimmune hepatitis?
- hemolytic anemia
- celiac sprue
- DM I
(all of these are autoimmune)
Tx of autoimmune hepatitis?
- corticosteroids for sx disease
risks/complications of steroids:
- short term: HTN, high glucose, psychosis, insomnia, gastric irritation
- long term: osteoporosis, cataracts, PUD, immunosuppression
- azathioprine - 2nd line agent
What is hemachromatosis?
- genetic disease due to autosomal recessive
- identified gene: HFE
- most common single gene disorder:
10% caucasians heterozygous
0.5% caucasians homozygous
very rare in other pops
PP of hemochromatosis?
- gene defect results in increased iron absorption in the intestinal tract from the diet
- iron overload in the body
- eventual fibrosis and organ failure:
Hematochromatosis - iron overload in the body? Why do females have delayed sxs?
- normal Fe: 3-4 mg/day
- normally Fe storage is controlled so there is no excess accumulation
- accum of 500-1000 mg/yr occurs in hemochromatosis
- sxs usually occur around age 40 or when Fe stores reach 15-40 g
- females have delayed sxs b/c of menstruation and breast feeding
Clinical manifestations are influenced by what factors?
- alcohol use
- dietary iron
- menstruation and breast feeding
- unkown factors
- alcohol abuse and hep C accelerate the process
- classic presentation: cutaneous hyperpigmentation w/ diabetes and cirrhosis
Reversible manifestations of hemochromatosis?
infections - cardiomyopathy (vibrio vulnificus)
conduction of disturbances
abdominal pain, elevated LFTs, hepatosplenomegaly
bronzing (melanin deposition)
grayness (Fe deposition)
Irreversible manifestations of hemochromatosis?
- liver: cirrhosis, HCC
- anterior pituitary gland: gonadotropin insufficiency- hypogonadism
- pancreas: DM (30-60%)
- thyroid: hypothyroidism
- genitalia: primary hypogonadism
- jts: pseudogout
- combo of:
lab: elevated serum transferrin sat of more than 45%, elevated serum ferritin (this is pathologic)
- confirmation = gold std = liver bx (also defines extent of disease)
- education for evidence of iron overload/complications:
avoid red meat, Fe supps
avoid handling or eating raw seafood (increased risk of infections)
receive vaccinations for Hep A and B
- mainstay of tx: phlebotomy:
removing 500 ml of blood removes 250 mg iron
- do weekly until iron depletion:
Hgb = 10-12 gm/dl
ferritin less than 50
transferritin sat is less than 50%
- maintenance: phlebotomy q 2-4 months
Genetic testing for hemochromatosis?
- screen 1st degree relatives, unless under 18
- likely to uncover homozygotes who are asx
- screening test cost: $200, done on whole blood sample
What is Wilson's disease?
- hepatolenticular degeneration
- autosomal recessive
- affects copper metabolism
- organ damage due to copper build up in liver and brain
- easily tx if dx early
- difficult to dx
Epidemiology and pathogenesis of Wilson's disease?
- occurs worldwide: prevalence - 1/30,000 live births
- 1/90 persons carry the abnormal gene ATP7B
gene affects the carrier protein of copper which is primarily in hepatocytes
- it also impairs the excretion of copper via bile
Clinical manifestations of Wilson's?
- presentation varies widely and is often non-specific
- generally presents b/t 1st-3rd decade:
liver disease (usually presenting sx in young kids)
Dx and prognosis of Wilson's
24 hr urine for copper excretion
look for kayser fleischer rings in eyes
universally fatal if left untx
once dx chelation therapy with D-penicillamine is toc (lifelong)
What are the 3 stages of alcoholic liver disease?
- fatty liver (steatosis)
- alcoholic hepatitis
- alcoholic fibrosis and cirrhosis
Fatty liver - etiology, presentation, labs?
- most pts are asx
- can occur w/in hours of large alcohol binge and if continues to drink - it can progress
- may have tender hepatomegaly
- transaminases mildly elevated
- can also occur in obese individuals and pregnancy
alcoholic hepatitis presentation?
- asx to extremely ill
- anorexia, N/V, wt loss, abdominal pain, poor nutritional status
fever is common
PE of alcoholic hepatitis?
- spider angiomas
- palmar erythema
- parotid enlargement
- testicular atrophy
Lab findings in alcholic hepatitis?
- leukocytosis w/ left shift (in severe disease)
- anemia: most likely be macrocytic from B12 and folate deficiency, may have microcytic from GI blood loss
- transaminases elevated: AST:ALT ratio usually greater than 2:0 (ratio rarely seen in other forms of liver disease)
- increased AP (less than 3x the normal)
- hyperbilirubinemia (60-90%) - jaundice
- hypoalbunemia (severe disease)
- coagulopathy (severe)
- elevated ammnonia level (severe)
Complications of alcoholic LD?
- alcoholic fatty liver is reversible
- alcoholic hepatitis: is usually reversible, but may run a fulminant course progressing to fibrosis and death
- long standing alcoholic liver disease can lead to cirrhosis
When do you see mallory bodies?
- when protein filaments are damaged in hepatocytes, appear pink on stain
- primarily seen with alcholic LD and wilsons
- will also see in HCC, even morbid obesity, assoc with severe liver disease
Tx of alcoholic LD?
- cessation of alcohol!!
- supportive tx:
B12 and folate
R/O other causes for fever, liver disease such as Hep C, hemochromatosis, neoplasms
glucocorticosteroids for severe hepatitis
- liver transplant in approp pts
What are factors influencing toxicity in toxic hepatitis?
- excessive intake
- excessive cytoP450 activity
- decrease metabolism pathways in liver
- depletion of glutathione stores
- concomitant use of alcohol or other drugs
- comorbid illness
- advancing age
- nutritional status
Prevalence of drug-induce liver injury (DILI)?
- annual incidence w/ prescription meds 1/10,000
- DILI accounts for 10% of all adverse drug rxns
- ****DILI most common cause of liver failure in the US
- over 1000 meds and herbal products have been implicated in development of DILI
Level of injury of DILI?
- many drugs induce asx elevations in liver enzymes w/o causing disease
- DILI most common liver injury caused by drugs and accounts for 10% of all cases of acute hepatitis
- may be cholestasis, cytotoxic or mixed, less likely steatosis
- usually d/c of agent results in complete recovery
Most common drugs implicated in DILI in US?
Tx for acetaminophen overdose?
- get an acetaminophen level
- activated charcoal if ingested w/in 2-3 hrs
- N-acetylcysteine for severe overdose
Signs and sxs of chronic acetaminophen intoxication? What pts are at the greatest risk for developing hepatotoxicity?
- signs and sxs are nonspecifc: confused w/ viral dx
- ask about acetaminophen usage, dosing
pts who are at greater risk for developing hepatotoxicity:
-ingestion of more than 7.5-10g over 24 hrs
-ingestion of less than 4 g with increased susceptibility
- liver tenderness, jaundice or ill-appearing
-supratherapeutic acetaminophen concentrations (over 20 mcg/mL)
Tx with NAC is recommended for which pts?
- all pts with liver tenderness and
- elevated aminotransferases and
- serum acetaminophen concentrations over 10 mcg/mL
- if serum acetaminophen concentrations are potentially toxic by the nomogram
General presentation of HAV, HBV, HCV, HEV?
- many cases can be asx especially in kids
- usually prodrome after exposure:
malaise and fatigue
pale stools, dark urine
General signs of Hepatitis infection on exam?
- RUQ pain
- +/- hepatomegaly
Labs in Hepatitis infection?
- transaminases elevated, usually in 1000s with ALT more increased than AST
- AP mildly elevated
- WBC normal to low
- may have prolonged PT
Acute viral hepatitis management?
- supportive care
- manage sxs
- no other liver toxins:
avoid exposure to other hepatitis viruses
- prevention: immunize HAV, HBV
What kind of virus is Hep A?
Prevalence of HAV? Chronic infection?
- infection occurs worldwide
- incidence in US decreased substantially since vaccine initiated
- no chronic infection
HAV routes of transmission?
- fecal-oral route predominates
- close personal contact (household contact, sex contact, day car centers)
- contaminated food/water
- blood exposure
- maternal-fetal transmission hasn't been reported
What does a IgG antiHAV level tell you?
- the pt has either had HAV for 6 months or they have been vaccinated
What is the HAV vaccination?
- inactivated vaccine
- part of childhood vaccination series
- SE: fever, injection site rxns, rash, HA
- regimen: 2 doses 6-12 months apart
- persons with clotting factor disorders or chronic liver dz
- users of illegal drugs
- those traveling to countries with high or intermediate levels
- any person wishing to obtain immunity
Postexposure prophylaxis HAV?
- hep A vaccine or IG
close personal contact
sharing IV drug apparatus
child care centers
schools, hospitals, other work settings
What type of virus is HBV?
- DNA, much more complicated than A
- est that there are more than 300 mill HBV carriers in the world
- US 125 mill infected
- over 350,000 deaths worldwide annually
- figures keep changing
HBV modes of transmission?
- sexual contact:
sexual spread major mode of transmission in developed countries:
heterosexual spread in US 39% new HBV infection
MSM 24% new HBV infections
major mode in underdeveloped countries
most infections occur at or near birth
- found in breast milk, but not a cause of transmission
nosocomial (Most commonly blood born infection in hosp setting)
- organ transplantation
- transfusions: very, very rare
- hepatitis vaccine
- post-exposure prophylaxis: give first dose of vaccine
administer HBIG at same time - diff site than vaccine
Clinical outcomes of acute HBV infections?
- 90% will resolve
- 9% will go on to have HBAg+ for greater than 6 mo - 50% of these will go on to resolve, the other 50% will either become asx carriers, chronic peristent hepatitis, or chronic active hepatitis - which can lead to cirrhosis, HCC, extrahepatic disease
- other 1% will go into fulminant hepatitis right a way
Signs and sxs of chronic HBV infection?
- many pts are asx
-exacerbations similar to acute infection
What are the extrahepatic manifestations of chronic Hep B?
- 10-20% due to circulating immune complexes:
When does HbsAg appear? What does HbcAg indicate?
appears prior to onset of sxs
resolved infection becomes undetectable in 4-6 months
- persistence past 6 m = chronic infection
intracellular ag in affected hepatocytes, presence of Anti-HBc of IgM class indicates acute infection
When will you see anti-HBsAb?
- follows disappearance of HBsAg
- usually persists for life
- when coexists with HBsAg these persons are regarded as carriers of HBV
- presence of anti-HBs only, indicates immunity by vaccination
What is HbeAg a marker of?
- secretory protein
- marker of HBV replication and infectivity
- HBeAg to anti-HBe occurs early in pts with acute infection
- seroconversion is delayed for years in pts with chronic HBV, when they do seroconvert usually means remission of their disease
What are HBV DNA assays used for?
- used to assess HBV replication
- recovery from HBV assoc with disappearance of HBV DNA
- major role is in pts with chronic HBV to monitor for need for tx and response to tx
Tx for chronic HBV infection?
- interferon or peginterferon is agent of choice
- pts who show evidence of viral replication are candidates for therapy:
HBeAg + pts
high serum HBV DNA levels
active liver disease (chronic hepatitis on liver bx) or elevated LFTs
- pts who have decompensated cirrhosis or are carriers shouldn't receive txs
SEs of peginterferon?
- flu-like sxs
- abdominal pain, N/V, dry mouth
- hair loss
- blurred vision
- going to be on this for 9 months
Other meds for tx Hep B?
- 1. Hep B easily becomes resistant so often a combo has been used
-2. tx is for months
- 3. meds are complicated and have multiple side effects so refer to specialist
A pt presents with these lab serologies:
IgM anti-HBc +
what does this pt have?
acute HBV infection
A pt presents with following lab results:
HBsAg + (greater than 6 mo)
HBV DNA +
ALT and AST moderately elevated ALT more than AST
- what does this pt have?
-chronic HBV infection
- fallen from 230,000/year in 80s to current level 19,000 cases in 2006
- one of the most common chronic liver diseases
- majority of liver transplants in US are for chronic HCV
Transmission of HCV?
- highest rate: IVDU/having sex with IVDU
- having been in jail for more than 3 days
- religious scarification
- blood transfusion - since routine testing risk very low
- having been struck or cut with blood object
- pierced ears or body parts
- immunoglobulin injection
- perinatal transmission can occur
- solid organ transplant
Who should be screened for HCV?
- ever injected illegal drugs
- received clotting factors made b/f '87
- received blood/organs b/f july 1992
- were ever on chronic hemodialyis
- have evidence of liver disease (increased ALT)
- are infected with HIV
- healthcare workers after needle stick/mucosal exposure to HCV + blood
- children born to HCV + mothers
Natural hx of HCV?
- 20% will recover
- 80% will go on to have a persistent infection, of this %, 30% will have stable chronic hepatitis, 40% will have variable progression, and 30% will have severe progression
Chronic HCV infection presentation?
- 80-100% pts remain HCV RNA positive
- 60-80% have persistently elevated liver enzymes
most common complaint is fatigue, sxs are rarely incapacitating, but may lead to a decrease in quality of life
- HCV accounts for 1/3 of HCC cases in US
- HCV RNA rises within 8 days to 8 wks following exposure
- anti-HCA is + within 12 weeks after exposure
- sometimes difficult to distinguish acute from chronic as both HCV RNA and anti-HCV are present in both
- chronic infection - have it for 6 or more months
Management of chronic HCV?
- assess for severity of disease
- tx as indicated
- counsel to reduce further harm to liver - no drinking, drugs
-if not already done vaccinate against A and B
PT selection for therapy for chronic HCV?
- selection criteria where therapy is widely accepted
- some criteria where therapy is considered
- pt criteria where therapy is CI
- pt eval for therapy:
liver bx - almost all pts undergo this
test for HIV
eval for other types of liver disease
continued IVDU or alcohol abuse
Tx for chronic HCV infection?
- combo of antivirals:
- assessing tx response:
HCV RNA negativity
sustained response HCV RNA negativity 6 months after tx is stopped
SEs of peg interferon/ribavirin?
- bone marrow suppression
- myalgias, HAs, low grade fevers - common 1st 48hrs after infusion
- neuropsych sxs (irritability) - must screen for depression
- non-productive cough and dyspnea
- ocular: ischemic retinopathy, retinal hemorrhage - eval by ophtho
- thyroid dysfxn: monitor
- rash, hair loss, hearing loss, insomnia
What protease inhibitor shows promise for tx HCV? Downside?
- Harvoni - tablet of 2 protease inhibitors that are showing promise but super expensive
- many side effects: including death!
Liver transplant process in HCV pts?
- non-infected liver transplanted into HCV infected pt becomes infected and decreases survival
- tx with peginterferon + ribavirin may prolong survival
- using a younger liver or a liver that is already HCV infected seems to help
Why is HDV unique? RNA or DNA?
- requires HBV for replication (must have HBV first)
- HBsAg coat
- single stranded RNA rod-like structure
small HDAg activates replication of HDV RNA in hepatocyte
large HDAg directs packaging HD virion into HBsAg
lipoprotein envelope is provided by HBV
Genotypes of HDV?
- genotype 1:
increased risk of fulminant course when compared to acute HBV, progression towards cirrhosis is rapid
- genotype 2: far East
- genotype 3: Venezuela, Columbia, Brazil, Peruvian and Amazon bases
- 5 other genotypes known
Transmission of HDV?
- close personal contact
- multiple transfusions
- contaminated dialysis equipment
10% HBV pts have HDV
HDV may be cytotoxic
Coinfections: HBV and HDV?
- coinefction w/ HBV: severe acute disease B+D, usually self limited (direct cytopathic damage)
low risk of chronic infection
- superinfection on top of chronic HBV:
usually develop chronic HDV infection, HBV suppressed
high risk of severe, progressive chronic liver disease (immune damage)
HDV prevention and tx?
- HBV vaccination
- HBV-HDV coinfection:
pre- or post-exposure prophylaxis to prevent HBV infection (immunoglobulin and vaccine)
- chronic HDV tx with peginterferon
What kind of virus is HEV? How is it transmitted? Is there a chronic form?
- enterically transmitted, waterborne virus, spread by fecally contaminated water, person to person transmission is rare
- can be transmitted via blood transfusion in endemic areas
- can be transmitted from mother to newborn
- US cases usually have travel hx to HEV endemic area
- no chronic form
What is HGV?
-- GB virus type C (GBV-C)
- HGV was initially cloned from a surgeon
- 2 diff agents isolatedL A, B, C - C is identical to HGV
- high incidence in US
- flavivirus - can be spread through contaminated blood and sxual contact
- evidence suggests that it doesn't cause hepatitis in humans
- protective effect on pts coinfected w/ HIV
What are complications of acute hepatitis?
- cholestatic hepatitis
- raging fulminant hepatitis
- chronic hepatitis
How do you dx chronic hepatitis?
- disease staging b/f tx
- f/u after tx
- typical progression:
chronic inflammation in portal areas
necrosis/inflammation (moderate activity)
fibrosis (marked activity)
What hepatitis viruses can cause chronic hepatitis?
- B, C, D
- fulminant: all except G
What is cirrhosis?
- development of fibrosis of liver with formation of regenerative nodules; results in impairment of synthetic, metabolic, and hemodynamic fxns of the liver
How do you dx cirrhosis?
- imaging studies: US, CT, MRI can SUGGEST dx
- Bx is GOLD std
- determine underlying etiology using Hx and labs:
Etiologies of cirrhosis?
- alcohol and chronic HCV in US account for 1/2 of transplant pts
- 10-15% are cryptogenic (dx of exclusion)
- primary biliary cirrhosis (PBC)
- chronic HBV
- wilson's disease
- nonalcoholic steatohepatitis
PP of cirrhosis?
- process of scarring of the liver
- normally the extracellular matrix has diff types of collagen and glycoproteins that are in balance
- as chronic insult to the liver persists over years the collagen production in the liver increases 4-10 fold
- the ECM becomes stiffer and normal fxns of the liver are compromised
- the change in the ECM affects hepatic stellate cells
- early fibrotic changes are reversible, as progression occurs the change becomes irreversible
Lab abnormalities in cirrhosis?
- aminotransferases: AST/ALT: moderately elevated
- AP: elevated but less than 2-3x normal, higher elevations suspect primary sclerosing cholangitis or PBS
- bilirubin: level rise as cirrhosis progresses
- albumin: levels fall as cirrhosis worsens
- PT: increases as ability of cirrhotic liver to synthesize clotting factors diminishes
- serum Na: hyponatremia seen with ascites
high levels of ADH - because of portal HTN - taking protein into abdomen, and fluid is following, less amt of fluid in vasculature - so secrete more ADH to hold onto more fluid
more lab abnormalities in cirrhosis - hematologic?
- thrombocytopenia: usually first, secondary to HTN and attendant congestive splenomegaly
- leukopenia: hypersplenism with margination
acute/chronic GI blood loss
folate deficiency (occurs early in malnutrition, B12 def occurs much later)
bone marrow suppression
anemia of chronic disease (Inflammation)
Why will there likely be portal HTN in cirrhosis?
- increased BP in portal vein due to increased resistance to blood passing through vessels in liver
- results in:
enlarged abdominal wall vessels (caput medusa), hemorrhoids
ascites (protein rich fluid)
How can we manage portal HTN?
- temp measures: remove ascitic fluid
- portal shunts
- tx liver disease
- liver transplant
What can hepatic encephalopathy lead to?
- potentially reversible neuropsych abnormalities:
motor impairment, including focal near findings
- syndrome observed in pts with cirrhosis:
prereq is a diversion of portal blood to systemic circulation, can occur in pts w/o cirrhosis who have surgically created portosystemic shunts
What other precipitating causes of HE need to be ruled out before you blame it cirrhosis?
- GI bleed
- hypokalemia/metabolic alkalosis
- sedatives or tranquilizers
- infection (SBP)
- rarely hepatoma or vascular occlusion
How do you grade the severity of HE?
- west-haven classifciation system:
- glasgow coma scale may be used in severe HE
How do you dx HE?
- ammonia and manganese are neurotoxins that precipitates HE
- serial ammonia levels are inferior to clinical assessment in gauging improvement or deterioration in pt who is being tx for HE
- EEG findings are not specific to HE, but if seizure activity needs to be ruled out an EEG may be helpful
- CT and MRI are helpful in ruling intracranial lesions
How do you tx HE?
- determin stage of HE
- exclude nonhepatic casues of alt mental fxn
- need to lower ammonia levels: for overt HE use
give enough so that the pt has 3-4 soft stools a day
SE: abdominal cramping, bloating, flatulence, enemas, electrolyte abnormalities
- severe SEsL ileus and hypovolemia to pt of worsening HE
- correct hypokalemia if present
- low protein diet may be helpful
-rifampin orally effects the metabolic fxn of the gut microbiota and is effective as laculose but with less SEs
- for more severe HE the pt may be at risk of aspiration and may need to be intubated